Geodesic
Spatial Dynamics of Contact-Activated Fibrin Clot Formation in vitro and in silico in Haemophilia B: Effects of Severity and Ahemphil B Treatment
A. A. Tokarev1 ; Yu. V. Krasotkina1 ; M. V. Ovanesov1, 2 ; M. A. Panteleev1 ; M. A. Azhigirova3 ; V. A. Volpert4 ; F. I. Ataullakhanov1, 5, 6 ; A. A. Butilin5
1 Laboratory of Physical Biochemistry of Blood, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167
2 Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore MD 21287
3 Laboratory of Blood Plasma Protein Fractionation, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167
4 Institute of Mathematics, University Lyon 1, Villeurbanne, France 69622
5 Faculty of Physics, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119992
6 Center for theoretical problems of physical-chemical pharmacology, Russian Academy of Sciences, 4 Kosygin Street, Moscow, Russia, 117977
Mathematical modelling of natural phenomena, Tome 1 (2006) no. 2, pp. 124-137

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Spatial dynamics of fibrin clot formation in non-stirred system activated by glass surface was studied as a function of FIX activity. Haemophilia B plasma was obtained from untreated patients with different levels of FIX deficiency and from severe haemophilia B patient treated with FIX concentrate (Ahemphil B) during its clearance with half-life t1/2=12 hours. As reported previously (Ataullakhanov et al. Biochim Biophys Acta 1998; 1425: 453-468), clot growth in space showed two distinct phases: activation and propagation. The activation phase is characterized by the time required to start clot growth from the activator, while the characteristic parameter of the propagation phase is the clot elongation rate. This rate reaches steady state in approximately ten minutes after the beginning of growth. In haemophilia B plasma, clot formation is substantially impaired: clot starts to grow from the activating surface later than in healthy donor plasma, and its propagation rate is considerably lower. The most significant abnormalities in clot growth kinetics are observed at FIX activity below 10% of normal. Simulation of these experiments was performed theoretically using a detailed biochemical model (Panteleev et al. Biophys J 2006; 90: 1489-1500) adapted for experimental conditions used. Suitability of the assumptions used to describe triggering contact activation was verified.
DOI : 10.1051/mmnp:2008007

A. A. Tokarev 1 ; Yu. V. Krasotkina 1 ; M. V. Ovanesov 1, 2 ; M. A. Panteleev 1 ; M. A. Azhigirova 3 ; V. A. Volpert 4 ; F. I. Ataullakhanov 1, 5, 6 ; A. A. Butilin 5

1 Laboratory of Physical Biochemistry of Blood, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167
2 Division of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 N Wolfe Street, Baltimore MD 21287
3 Laboratory of Blood Plasma Protein Fractionation, National Research Center for Hematology, Russian Academy of Medical Sciences, 4a Novii Zykovskii Proezd, Moscow, Russia 125167
4 Institute of Mathematics, University Lyon 1, Villeurbanne, France 69622
5 Faculty of Physics, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119992
6 Center for theoretical problems of physical-chemical pharmacology, Russian Academy of Sciences, 4 Kosygin Street, Moscow, Russia, 117977 
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     title = {Spatial {Dynamics} of {Contact-Activated} {Fibrin} {Clot} {Formation} in vitro and in silico in {Haemophilia} {B:} {Effects} of {Severity} and {Ahemphil} {B} {Treatment}},
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A. A. Tokarev; Yu. V. Krasotkina; M. V. Ovanesov; M. A. Panteleev; M. A. Azhigirova; V. A. Volpert; F. I. Ataullakhanov; A. A. Butilin. Spatial Dynamics of Contact-Activated Fibrin Clot Formation in vitro and in silico in Haemophilia B: Effects of Severity and Ahemphil B Treatment. Mathematical modelling of natural phenomena, Tome 1 (2006) no. 2, pp. 124-137. doi: 10.1051/mmnp:2008007

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